Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells

We have shown previously that KIAA0223, a gene encoding a minor histocompatibility antigen, HA-1, whose expression was believed to be restricted to the hematopoietic cells, is aberrantly expressed in some solid tumor cell lines. However, its significance in tumor immunity needs to be determined. Cytotoxic activity of HA-1H-specific cytotoxic T lymphocytes (CTLs) was assessed against solid tumor cell lines expressing KIAA0223 using 51Cr release assays. Five of seven cell lines were lysed when HLA-A*0201 was adequately expressed. One of the two CTL-resistant cell lines became susceptible after treatment with IFN-γ and TNF-α, while the other was lysed only after pulsing with HA-1H peptide. In most cell lines tested, HA-1H peptide was properly generated and presented for recognition by the CTL. However, impaired antigen processing and presentation observed in this study may result in escape from CTL recognition in vivo, as well as in vitro, as observed in this study.